The role of the endogenous cannabinoid system in ethanol self-administration

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DESCRIPTION (provided by applicant): The general objective of this project is to explore the neurobiological mechanisms responsible for the escalation and maintenance of ethanol self-administration. Current theories of addiction posit that long-term ethanol self-administration becomes a habit-based, rather that goal-oriented, behavior. Neuroplasticity in the dorsolateral striatum is thought to be necessary for the expression of habitual behavior, and recent research implicates the endocannabinoid system in both habit formation and in several forms of striatal plasticity. Thus, the overarching hypothesis of this proposal is that the maintenance of long-term ethanol self-administration is a habit-based behavior mediated, at least in part, by endocannabinoid signaling in the dorsolateral striatum. This hypothesis will be tested in the two specific aims of the present application. The first aim will measure the effect of operant ethanol self-administration by Long Evans rats on extracellular levels of the two endocannabinoids anandamide and 2-AG, as measured by in vivo microdialysis, in the dorsolateral striatum. The second aim will examine the involvement of the cannabinoid CB1 receptor during the expression of habitual operant ethanol self-administration in Long Evans rats. After establishing self- administration of ethanol, rats will receive infusions of the CB1 receptor antagonist rimonabant into the dorsolateral striatum to determine the involvement of these receptors in self-administration behavior. Together, the results of these experiments should increase the understanding of the role of the endocannabinoid system in habitual ethanol self-administration, and contribute new information regarding the mechanisms that underlie the maintenance of habitual self-administration of alcohol. Public health relevance: The present study aims to investigate neurobiological mechanisms underlying the development and maintenance of behaviors involved in alcohol addiction. The information gained from this research will lead to a better understanding the brain changes that occur as chronic alcohol use develops, and could be used to develop more effective treatments for alcohol addiction.